The major objective of this research is to study the postulated association between CLL and chronic antigenic stimulation (related to infections, inflammatory processes and autoimmune diseases) by means of medical chart review and interview in a case-control study. We are also exploring the postulated increased familial incidence of CLL and other lymphoproliferative malignancies. We are examining possible associations of CLL with occupation, smoking, alcohol use, immunizations and operative procedures involving the lymphoproliferative system (tonsillectomy, splenectomy, etc.) in order to develop additional etiologic hypotheses. A medical record room search of all Baltimore SMSA hospitals is one of the prime sources for ascertaining cases. Physicians have reviewed 339 charts at 2 of the 3 major university hospitals and 2 of the largest community hospitals where a large proportion of CLL cases are expected to have been seen. At present, this has yielded 121 cases diagnosed as CLL. Actually, 11/121 (9%) cases called CLL did not meet the criteria for CLL as established by the NCI CLL/Myeloma Task Force because of absolute lymphocyte counts less than 15,000/mm3. 28/121 (23%) of cases called CLL are probably cases of well-differentiated lymphocytic lymphoma. Each case is matched with two controls with any malignancy other than a lymphoproliferative neoplasm and two controls with any non-malignant disease. The matching variables include age (within 5 years), sex, race, date of diagnostic admission and hospital of admission. We have just begun the interview and blood-drawing portion of the study. We hope to identify differences of HLA types between patients with CLL and controls. We will then attempt to correlate these differences with epidemiologic and clinical characteristics of the various subgroups of our population of cases and controls.